Design and synthesis of drug hydrogels containing carboxymethylcellulose with honeycomb structure and pH-sensitivity as drug delivery systems for adriamycin, metformin, and naproxen.

The aim of this research is to prepare and identify functionalized carboxymethylcellulose/mesoporous silica nanohydrogels (CMC/NH2-MCM-41) for obtaining a pH-sensitive system for the controlled release of drugs. The beads of CMC/NH2-MCM-41 nanocomposites were prepared by dispersing NH2-MCM-41 in a CMC polymer matrix and crosslinking with ferric ions (Fe3+). The SEM analysis of samples revealed enhancement in surface porosity of the functionalized nanohydrogel beads compared to the conventional beads. Swelling of the prepared functionalized nanohydrogels was evaluated at various pH values including pH = 7.35-7.45 (simulated body fluid or healthy cells), pH = 6 (simulated intestinal fluid), and pH = 1.5-3.5 (simulated gastric fluid). The swelling of CMC/MCM-41 and CMC/NH2-MCM-41 nanohydrogels at the pH values of simulated body fluid and simulated intestinal fluid is much higher than that of simulated gastric fluid, indicating successful synthesis of pH-sensitive nanohydrogels for drug delivery. The drug loading results showed that drug release in the CMC/NH2-MCM-41 system is much slower than that in the CMC/MCM-41 system. The results of the survival studies for the manufactured systems showed a very good biocompatibility of the designed drug delivery systems for biological applications. By coating the surface of functionalized mesopores with CMC hydrogel, we were able to develop a pH-sensitive intelligent drug delivery system.

Corrigendum: Yolk@Wrinkled-double shell smart nanoreactors: new platforms for mineralization of pharmaceutical wastewater.

[This corrects the article DOI: 10.3389/fchem.2023.1211503.].

In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom.

In this study, we investigated the potential in vitro anti-HSV-1 activities of the Cassiopea andromeda jellyfish tentacle extract (TE) and its fractions, as well as computational work on the thymidine kinase (TK) inhibitory activity of the identified secondary metabolites. The LD50, secondary metabolite identification, preparative and analytical chromatography, and in silico TK assessment were performed using the Spearman-Karber, GC-MS, silica gel column chromatography, RP-HPLC, LC-MS, and docking methods, respectively. The antiviral activity of TE and the two purified compounds Ca2 and Ca7 against HSV-1 in Vero cells was evaluated by MTT and RT-PCR assays. The LD50 (IV, mouse) values of TE, Ca2, and Ca7 were 104.0 ± 4, 5120 ± 14, and 197.0 ± 7 (µg/kg), respectively. They exhibited extremely effective antiviral activity against HSV-1. The CC50 and MNTD of TE, Ca2, and Ca7 were (125, 62.5), (25, 12.5), and (50, 3.125) µg/ml, respectively. GC-MS analysis of the tentacle extract revealed seven structurally distinct chemical compositions. Four of the seven compounds had a steroid structure. According to the docking results, all compounds showed binding affinity to the active sites of both thymidine kinase chains. Among them, the steroid compound Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis(oxy)]-, cyclic 3-(1,2-ethane diyl acetal) (Ca2) exhibited the highest affinity for both enzyme chains, surpassing that of standard acyclovir. In silico data confirmed the experimental results. We conclude that the oxosteroid Ca2 may act as a potent agent against HSV-1.

Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.

This study set out to evaluate the wound healing properties of brittle star extracts in vitro and in vivo. Due to the great arm regeneration potential of the brittle star, Ophiocoma cynthiae, the present study aimed to evaluate the wound healing effect of hydroalcoholic extracts of brittle star undergoing arm regeneration in wound healing models. The brittle star samples were collected from Nayband Bay, Bushehr, Iran. After wound induction in the arm of brittle stars, hydroalcoholic extracts relating to different times of arm regeneration were prepared. The GC-MS analysis, in vitro MTT cell viability and cell migration, Western blot, and computational analysis tests were performed. Based on the in vitro findings, two BSEs were chosen for in vivo testing. Macroscopic, histopathological and biochemical evaluations were performed after treatments. The results showed positive proliferative effects of BSEs. Specifically, forty-two compounds were detected in all groups of BSEs using GC-MS analysis, and their biological activities were assessed. The MTT assay showed that the 14 d BSE had a higher proliferative effect on HFF cells than 7 d BSE. The cell migration assay showed that the wound area in 7 d and 14 d BSEs was significantly lower than in the control group. Western blot analysis demonstrated an increase in the expression of proliferation-related proteins. Upon the computational analysis, a strong affinity of some compounds with proteins was observed. The in vivo analysis showed that the evaluation of wound changes and the percentage of wound healing in cell migration assay in the 7 d BSE group was better than in the other groups. Histopathological scores of the 7 d BSE and 14 d BSE groups were significantly higher than in the other groups. In conclusion, the hydroalcoholic extract of O. cynthiae undergoing arm regeneration after 7 and 14 days promoted the wound healing process in the cell and rat skin wound healing model due to their proliferative and migratory biological activity.

Yolk@Wrinkled-double shell smart nanoreactors: new platforms for mineralization of pharmaceutical wastewater.

Nanomaterials with "yolk and shell" "structure" can be considered as "nanoreactors" that have significant potential for application in catalysis. Especially in terms of electrochemical energy storage and conversion, the nanoelectrode has a large specific surface area with a unique yolk@shell structure, which can reduce the volume change of the electrode during the charging and discharging process and fast ion/electron transfer channels. The adsorption of products and the improvement of conversion reaction efficiency can greatly improve the stability, speed and cycle performance of the electrode, and it is a kind of ideal electrode material. In this research, heterojunction nanoreactors (FZT Y@WDS) Fe3O4@ZrO2-X@TiO2-X were firstly synthesized based on the solvothermal combined hard-template process, partial etching and calcination. The response surface method was used to determine the performance of the FZT Y@WDS heterojunction nanoreactors and the effects of four process factors: naproxen concentration (NAP), solution pH, the amount of charged photocatalyst, and the irradiation time for photocatalytic degradation of NAP under visible light irradiation. To maximize the photocatalytic activity, the parameters of the loaded catalyst, the pH of the reaction medium, the initial concentration of NAP, and the irradiation time were set to 0.5 g/L, 3, 10 mg/L, and 60 min, respectively, resulting in complete removal of NAP and the optimum amount was calculated to be 0.5 g/L, 5.246, 14.092 mg/L, and 57.362 min, respectively. Considering the promising photocatalytic activity of FZT Y@WDS under visible light and the separation performance of the nanocomposite, we proposed this photocatalyst as an alternative solution for the treatment of pharmaceutical wastewater.

Comparing the healing properties of intra-articular injection of human dental pulp stem cells and cell-free-secretome on induced knee osteoarthritis in male rats.

OBJECTIVE: Osteoarthritis (OA) is a common and painful joint disease with multifactorial causes. Stem cells, due to their high ability to reproduce and differentiate, have created a new horizon in tissue engineering of cartilage and bone. Secretions are one of the new therapies that can be used with stem cells or separately. This study aimed to compare the healing effects of human dental pulp stem cells, cell-free secretome, and human dental pulp mesenchymal stem cells with secretome in the induced OA in male rats. METHODS: Dental pulp mesenchymal stem cells were isolated and prepared from human dental pulp. The collagenase type II was injected into the knee of twenty-five male Sprague-Dawley rats, and after 10 weeks, OA was confirmed. Rats were divided into five groups (n = 5): 1) Human dental pulp stem cells plus secretome (HDP+Sec); 2) Human dental pulp stem cells (HDP); 3) Secretome (Sec); 4) Hyalgan as the positive control (Hya); 5) No treatment as the negative control (Ctrl). After 12 weeks since OA was confirmed, the healing process was examined by histopathology and radiology evaluations. RESULTS: Histopathological evaluations, radiological assessments, and matrix indexes in three treatment groups significantly improved compared to the Ctrl and Hya groups. Surface in HDP+Sec was significantly better than the Ctrl group. In radiological evaluations, a significant decrease in OA was observed in the three treatment groups in comparison with the Ctrl groups. There was no significant difference between the treatment groups in any radiological and histopathological evaluations. HDP + Sec group slightly records better results compared to Sec or HDP treatment groups. CONCLUSION: It was concluded that human dental pulp stem cells and their secretome promote cartilage regeneration due to their cell protective potential as well as matrix degeneration reduction capacity.

Effect of Health Promotion Interventions in Active Aging in the Elderly: A Randomized Controlled Trial.

Background: Active aging has been the paradigm of the old-age lifestyle. Integrated aging care interventions in health centers primarily focus on diseases such as diabetes, hypertension, depression, and cardiovascular diseases, and there is no program or training regarding active aging. This study was carried out from September to December 2021 to determine the effectiveness of an intervention program to promote active aging in the elderly referred to Mashhad health centers. Methods: This randomized controlled clinical trial was conducted on 60 elderly individuals without disabling diseases and cognitive impairment who presented to the Daneshamooz health center in Mashhad in 2021. Through a simple block allocation scheme, those who met the inclusion criteria were randomly divided into the intervention and control groups. The intervention group received the health promotion program during 6 sessions (one session per week) about nutrition, physical activity, responsibility, stress management, communications, and spiritual aspects. The data were gathered using the active aging questionnaire and analyzed using the SPSS software version 25; independent and paired t-test, Wilcoxon, and Mann-Whitney U tests were utilized. P value< 0.05 was considered statistically significant. Results: The results of this study demonstrated that after the intervention, the total active aging score in the intervention group increased significantly (68.5±3 to 85±8.25) (P<0.001) and there was a significant difference between the control and intervention groups (68±3.25 to 85±8.25) (P<0.001). Conclusion: According to the results, training based on a health-enhancement approach can effectively promote active aging in the elderly. Therefore, more attention should be paid to strategic planning for active aging in health centers.Trial Registration Number: IRCT20210308050639N.

Photocatalytic activity of ZrO2/TiO2/Fe3O4 ternary nanocomposite for the degradation of naproxen: characterization and optimization using response surface methodology.

In this study, ZrO2, TiO2, and Fe3O4 components were synthesized by co-precipitation, sol-gel, and co-precipitation methods, respectively. In addition, solid-state dispersion method was used for synthesizing of ZrO2/TiO2/Fe3O4 ternary nanocomposite. The ZrO2/TiO2/Fe3O4 nanocomposite was characterized by different techniques including XRD, EDX, SEM, BET, FTIR, XPS, EELS, and Photoluminescence (PL). The FTIR analysis of ZrO2/TiO2/Fe3O4 photocatalyst showed strong peaks in the range of 450 to 700 cm-1, which represent stretching vibrations of Zr-O, Ti-O, and Fe-O. The results of FTIR and XRD, XPS analyses and PL spectra confirmed that the solid-state dispersion method produced ZrO2/TiO2/Fe3O4 nanocomposites. The EELS analysis confirmed the pure samples of Fe3O4, TiO2 and ZrO2. The EDAX analysis showed that the Zr:Ti:Fe atomic ratio was 0.42:2.08:1.00. The specific surface area, pores volume and average pores size of the photocatalyst were obtained 280 m2/g, 0.92 cm3/g, and 42 nm respectively. Furthermore, the performance of ZrO2/TiO2/Fe3O4 nanocomposite was evaluated for naproxen removal using the response surface method (RSM). The four parameters such as NPX concentration, time, pH and catalyst concentration was investigated. The point of zero charge of the photocatalyst was 6. The maximum and minimum degradation of naproxen using photocatalyst were 100% (under conditions: NPX concentration = 10 mg/L, time = 90 min, pH = 3 and catalyst concentration = 0.5 g/L) and 66.10% respectively. The stability experiment revealed that the ternary nanocatalyst demonstrates a relatively higher photocatalytic activity after 7 recycles.

Stability Risk Assessment of Underground Rock Pillars Using Logistic Model Trees.

Pillars are important structural elements that provide temporary or permanent support in underground spaces. Unstable pillars can result in rock sloughing leading to roof collapse, and they can also cause rock burst. Hence, the prediction of underground pillar stability is important. This paper presents a novel application of Logistic Model Trees (LMT) to predict underground pillar stability. Seven parameters-pillar width, pillar height, ratio of pillar width to height, uniaxial compressive strength of rock, average pillar stress, underground depth, and Bord width-are employed to construct LMTs for rock and coal pillars. The LogitBoost algorithm is applied to train on two data sets of rock and coal pillar case histories. The two models are validated with (i) 10-fold cross-validation and with (ii) another set of new case histories. Results suggest that the accuracy of the proposed LMT is the highest among other common machine learning methods previously employed in the literature. Moreover, a sensitivity analysis indicates that the average stress, p, and the ratio of pillar width to height, r, are the most influential parameters for the proposed models.

Single-bubble EHD behavior into water two-phase flow under electric-field stress and gravitational acceleration using PFM.

In this study, single-bubble electro-hydrodynamic effects on the two-phase laminar flow of water under electric field stress are investigated using numerical modeling. A 2D axisymmetric model is also developed to study the growth and departure of a single bubble. The phase-field method is applied to track the interphase between liquid and gas. The growth of the attached vapor bubble nucleus to a superheat at 7.0 °C and 8.5 °C are evaluated with 50° and 90° contact angles. The results show that the enhancement of the contact angle changes the velocity and temperature fields around the bubble. It is observed that the growing size and base of the bubble is increased with increasing the wall superheat, but the bubble departure diameter and time are decreased. The electric field results in raising the number of detached bubbles from the superheat at a certain time interval but decreasing the bubbles departure size. Additionally, the formation of stretched bubbles enhances the rate of heat flux and there is a non-linear relationship between the applied voltage and heat flux.

Extraction of ingredients from tea leaves using oxidative enzymatic reaction and optimization of extraction conditions.

Peroxidase (POD) and polyphenol oxidase (PPO) are used as biocatalyst in many processes such as oxidization reactions, wastewater treatment, phenol synthesis and so on. The purpose of current study is enzymes extraction from biomass (tea leaves) as well as evaluation of their activation. Different parameters including temperature, buffer concentration, buffer type, buffer/tea leaves ratio, addition of high molecular weight polymers and emulsifiers, and pH were optimized in order to obtain the highest enzymes activity. Response Surface Methodology (RSM) procedure is employed for statistical analysis of enzymes extraction. It is understood from the result that PPO and POD possess the highest activity at temperatures of 25 °C and 50 °C, pH 7 and 5, buffer molarity of 0.1, and 0.05, buffer/tea leaves ratio = 5 for both, contact time = 20 min and 10 min, and presence of 6% and 3% PVP, 5% and 0% Tween 80 for PPO and POD, respectively. Amounts of highest activity for PPO and POD biocatalysts were calculated 0.42 U/mL and 0.025493 U/mL, respectively. Moreover, the entire inactivation of PPO took place after 30 min at 40 °C and 60 °C and 20 min at 80 °C. However, POD lost 35% of its activity after 30 min at 40 °C and 60 °C. The amount of 6% POD activity was kept after 45 min at 80 °C. Generally, it was indicated that POD was more resistant to thermal treatment than PPO.

The Effect of Home Visit Program Based on the Continued Kangaroo Mother Care on Maternal Resiliency and Development of Premature Infant: A Randomized Clinical Trial.

BACKGROUND: Premature birth is a crisis for mothers and affects resilience. Premature babies are at risk for developmental disorders. The Kangaroo Mother Care (KMC) can reduce maternal stress and improve the growth of the baby. This study aimed at assessing the effect of home visit based on the continued KMC on maternal resiliency and development of premature infant. METHODS: This randomized controlled trial conducted on 50 pairs of mothers and premature babies with gestational age of 26-32 weeks who were admitted to Neonatal Intensive Care Unit of Om-al-Banin Hospital, Mashhad, Iran in 2019. The KMC is practiced routinely for all eligible newborns in this hospital. The experimental group continued the KMC one month after discharge at home and received two home visits. Resiliency of the mothers was assessed in admission, discharge, and one month after discharge with the Connor and Davison questionnaire and the development of the newborns was assessed in two months of adjusted age with Ages and Stages Questionnaire (ASQ). Data analysis was performed using SPSS software version 16 and t-test, Mann-Whitney, ANOVA, Friedman, Chi-square, Fishers exact. The significance level was set at P<0.05. RESULTS: The resiliency score of the mothers one month after discharge was112.50±5.50 and 76.40±5.60 in the experimental and control groups, which was significantly different (P<0.001). The ASQ development score of the newborns in two months of adjusted age was also significantly higher in the experimental than the control group (280.40±15.60vs223.80±22.00) (P<0.001). CONCLUSION: The results showed that the home visit program based on the continued KMC was effective in increasing maternal resilience and the development of premature infants. Trial Registration Number IRCT20181121041718N1.

Design and optimization of a hybrid process based on hollow-fiber membrane/coagulation for wastewater treatment.

Treatment of textile wastewater using ultrafiltration membranes was carried out in this study. Since membrane fouling is a major operational problem that decreases the membrane separation efficiency, wastewater was treated with polyaluminum chloride (PACl) and alum (aluminum sulfate) as coagulant to decrease the fouling of ultrafiltration membranes. PACl was selected as the best coagulant in the experiments. Also, chitosan was used as coagulant aid upon developing the hybrid process. The obtained optimum dosage of PACl coagulant was 100 mg/L, and maximum turbidity and COD removal of 35% and 66% were attained, respectively. The pretreated wastewater by coagulation was sent to ultrafiltration process for further removal of turbidity and COD. Three ultrafiltration hollow-fiber membranes made of polypropylene (PP), polyvinylidene fluoride (PVDF), and polyethersulfone (PES) were applied in this study. In general, the filtration results were evaluated for two types of samples treated under coagulation and without treatment; the results were unfavorable for the second type. The effects of transmembrane pressure (TMP) and cross velocity on membranes performance were also investigated for process optimization. The obtained results showed that PVDF membrane had the highest flux and turbidity removal, whereas the PES membrane had the highest COD removal. Also, the results revealed that turbidity and COD removal by all membranes were decreased by increasing TMP and cross velocity.

Preparation and optimization of activated nano-carbon production using physical activation by water steam from agricultural wastes.

Production of activated nano-carbon from agricultural wastes was studied in this work. To obtain the optimum production conditions by a physical activation method, influence of temperature (850, 900, 950 and 1000 °C), activation residence time (30, 60 and 90 min), and mill rotation (200, 300 and 400 rpm) were investigated using three different raw materials including walnut, almond and pistachio shells. To prepare activated nano-carbon, all the samples were heated up to the final activation temperature under a continuous steam flow of 130 cm3 min-1, and at a heating rate of 3 °C min-1, and were held at the different activation temperatures for 30, 60 and 90 minutes. BET surface area of the obtained activated carbons was measured from nitrogen adsorption data in the relative pressure range between 0 to 1. Activated nano-carbon standard indexes were evaluated according to the ASTM standard and the samples were compared. First, the cellulose raw material was heated in the carbonization furnace at 600 °C and then activated in the advanced activation furnace at a temperature between 850 to 1000 °C for 30, 60 and 90 minutes with water vapor. Ash percentage, iodine content, moisture content, specific area, elemental analysis, and FESEM were used for product characterization. The results of the analysis showed that by using the water vapor physical activation method and optimizing the parameters of this process including time and rotation of the mill up to 10 min and 400 rpm, resulted in a significant increase in specific surface area, cavity volume and the iodine number of the final product.

Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats.

AIMS: Doxorubicin, an antibiotic belonging to anthracycline family, has been used for treatment of malignancies. Cardiotoxicity is the main adverse effect of doxorubicin. Apigenin, as a flavonoid, has antioxidant, anti-inflammatory and anti-tumoral properties. The aim of this study was the assessment of any protective effect of apigenin on cardiotoxicity induced by doxorubicin. MAIN METHODS: 40 male Wistar rats were randomly divided into 4 groups: control, cardiotoxicity (DOX), apigenin treated group (DOX + Api 25) and apigenin group (Api 25). At the end of the experiment, the markers of cardiac function (%EF, %FS, LVIDs, LVIDd), cardiac and liver injury (LDH, CK-MB, cTn-I, ALT, and AST), cardiac apoptosis (Bax, Bcl-2 and Caspase3), cardiac oxidative stress (SOD, GSH, MDA) and cardiac fibrosis were measured. KEY FINDINGS: Apigenin improved cardiac functional parameters. The levels of cardiac and liver injury markers were significantly decreased in DOX + Api 25 compared to DOX. Treatment with apigenin caused significant decrease in percentage of cardiac fibrosis in comparison with DOX. Apigenin in DOX + Api 25 group led to significant decrease in apoptotic proteins (Casp3, Bax) and a significant increase in anti-apoptotic proteins (Bcl2). In apigenin treatment groups, SOD levels significantly increased while a significant decrease was observed in MDA. The amount of GSH in DOX + Api 25 had no significant change in comparison to control and Api 25 groups. SIGNIFICANCE: Apigenin reduced cardiac injuries induced by DOX through anti-fibrotic, antioxidant and anti-apoptotic properties. It seems that apigenin prevents cardiac injuries and improves cardiac function.

Association between anthropometric indices and quality of life in menopausal women.

OBJECTIVE: To investigate whether body mass index (BMI), abdominal obesity or fat distribution influence the quality of life of postmenopausal women. METHODS: Subjects in this cross-sectional study were 233 postmenopausal women (aged 45-70 years) with an intact uterus and ovaries and who were sexually active and not using hormone therapy. Anthropometric measurements were recorded and subjects were interviewed using a specific health-related quality of life (HR-QoL) instrument, the MENQoL scale. RESULTS: According to BMI values, 31.5% of the women were obese, 42.2% were overweight, 25.8% were normal weight and none were underweight. However, according to the MENQOL scale results, obese women scored significantly higher on symptoms for physical domains. The women with the android pattern of fat distribution had significantly higher scores in the vasomotor and physical domains (p < 0.05). CONCLUSIONS: Obesity did not affect global HR-QoL in postmenopausal women, but appeared to have an influence on the psychical domains. Other anthropometric measurements were not associated with differences in HR-QoL. Keeping the anthropometric indices in the normal/premenopausal might improve the quality of life in menopause women.

Reciprocal powered time model for release kinetic analysis of ibuprofen solid dispersions in oleaster powder, microcrystalline cellulose and crospovidone.

PURPOSE: A physically sound derivation for reciprocal power time (RPT) model for kinetic of drug release is given. In order to enhance ibuprofen dissolution, its solid dispersions (SDs) prepared by cogrinding technique using crospovidone (CP), microcrystalline cellulose (MC) and oleaster powder (OP) as a novel carrier and the model applied to the drug release data. METHODS: The drug cogrounds with the carriers were prepared and subjected to the dissolution studies. For elucidation of observed in vitro differences, FT-IR spectroscopy, X-ray diffraction patterns, DSC thermograms and laser particle size measurement were conducted. RESULTS: All drug release data fitted very well to newly derived RPT model. The efficiency of the carriers for dissolution enhancement was in the order of: CP>OP>MC. The corresponding release kinetic parameter derived from the model, t50% (time required for 50% dissolution) for the carrier to drug ratio 2:1 were 2.7, 10.2 and 12.6 min, respectively. The efficiency of novel carrier, OP, was between CP and MC. FT-IR showed no interaction between the carriers and drug. The DSC thermograms and X-ray diffraction patterns revealed a slight reduced crystallinty in the SDs. Also grinding reduced mean particle size of drug from 150.7 to 44.4 microm. CONCLUSIONS: An improved derivation for RPT model was provided which the parameter of the model, t50%, unlike to previous derivations was related to the most important property of the drug i.e. its solubility. The model described very well drug release kinetics from the solid dispersions. Cogrinding was an effective technique in enhancing dissolution rate of ibuprofen. Elaeagnus angostifolia fruit powder was suggested as a novel potential hydrophilic carrier in preparing solid dispersion of ibuprofen.